Shape memory is the ability of a material to remember its original shape, either after mechanical deformation (FIG. 1), which is a one-way effect, or by cooling and heating (FIG. 2), which is a two-way effect. This phenomenon is based on a structural phase transformation.
The first materials known to have these properties were shape memory metal alloys (SMAs), including TiNi (Nitinol), CuZnAl, and FeNiAl alloys. The structure phase transformation of these materials is known as a martensitic transformation. These materials have been proposed for various uses, including vascular stents, medical guidewires, sutures, orthodontic wires, vibration dampers, pipe couplings, electrical connectors, thermostats, actuators, eyeglass frames, and brassiere underwires. For example, U.S. Pat. Nos. 5,002,563, 5,766,218, and 5,281,236 describe various articles formed of shape memory alloys in various medical applications. Nonetheless, these materials have not yet been widely used, in part because they are relatively expensive.
Shape memory polymers (SMPs) are being developed to replace or augment the use of SMAs, in part because the polymers are light, high in shape recovery ability, easy to manipulate, and economical as compared with SMAs. In the literature, SMPs are generally characterized as phase segregated linear block co-polymers having a hard segment and a soft segment. The hard segment is typically crystalline, with a defined melting point, and the soft segment is typically amorphous, with a defined glass transition temperature. In some embodiments, however, the hard segment is amorphous and has a glass transition temperature rather than a melting point. In other embodiments, the soft segment is crystalline and has a melting point rather than a glass transition temperature. The melting point or glass transition temperature of the soft segment is substantially less than the melting point or glass transition temperature of the hard segment.
When the SMP is heated above the melting point or glass transition temperature of the hard segment, the material can be shaped. This (original) shape can be memorized by cooling the SMP below the melting point or glass transition temperature of the hard segment. When the shaped SMP is cooled below the melting point or glass transition temperature of the soft segment while the shape is deformed, a new (temporary) shape is fixed. The original shape is recovered by heating the material above the melting point or glass transition temperature of the soft segment but below the melting point or glass transition temperature of the hard segment. In another method for setting a temporary shape, the material is deformed at a temperature lower than the melting point or glass transition temperature of the soft segment, resulting in stress and strain being absorbed by the soft segment. When the material is heated above the melting point or glass transition temperature of the soft segment, but below the melting point (or glass transition temperature) of the hard segment, the stresses and strains are relieved and the material returns to its original shape. The recovery of the original shape, which is induced by an increase in temperature, is called the thermal shape memory effect. Properties that describe the shape memory capabilities of a material are the shape recovery of the original shape and the shape fixity of the temporary shape.
Several physical properties of SMPs other than the ability to memorize shape are significantly altered in response to external changes in temperature and stress, particularly at the melting point or glass transition temperature of the soft segment. These properties include the elastic modulus, hardness, flexibility, vapor permeability, damping, index of refraction, and dielectric constant. The elastic modulus (the ratio of the stress in a body to the corresponding strain) of an SMP can change by a factor of up to 200 when heated above the melting point or glass transition temperature of the soft segment. Also, the hardness of the material changes dramatically when the soft segment is at or above its melting point or glass transition temperature. When the material is heated to a temperature above the melting point or glass transition temperature of the soft segment, the damping ability can be up to five times higher than a conventional rubber product. The material can readily recover to its original molded shape following numerous thermal cycles, and can be heated above the melting point of the hard segment and reshaped and cooled to fix a new original shape.
Conventional shape memory polymers generally are segmented polyurethanes and have hard segments that include aromatic moieties. U.S. Pat. No. 5,145,935 to Hayashi, for example, discloses a shape memory polyurethane elastomer molded article formed from a polyurethane elastomer polymerized from a difunctional diiiosicyanate, a difunctional polyol, and a difunctional chain extender.
Examples of polymers used to prepare hard and soft segments of known SMPs include various polyethers, polyacrylates, polyamides, polysiloxanes, polyurethanes, polyether amides, polyurethane/ureas, polyether esters, and urethane/butadiene copolymers. See, for example, U.S. Pat. No. 5,506,300 to Ward et al.; U.S. Pat. No. 5,145,935 to Hayashi; U.S. Pat. No. 5,665,822 to Bitler et al.; and Gorden, “Applications of Shape Memory Polyurethanes,” Proceedings of the First International Conference on Shape Memory and Superelastic Technologies, SMST International Committee, pp. 115-19 (1994).
Current approaches for implanting medical devices, many of which are polymeric in nature, often require complex surgery followed by device implantation. With the advent of minimally invasive surgery (J. G. Hunter, Ed., Minimally invasive surgery (McGraw Hill, New York, 1993)), it is possible to place small systems down laprascopes. However, there remains a challenge for one to implant a bulky device and/or knot a suture in a confined space. Moreover, Established synthetic, degradable suture materials are mainly aliphatic polyhydroxy acids showing bulk degradation. This degradation process can be split into several stages (A. Lendlein, Chem. in unserer Zeit 33, 279 (1999)), the first three of which are swelling, loss in molecular weight, and loss in sample mass.
U.S. Pat. No. 6,281,262 B1 to Shikinami and EP 1000958 by Takiron Co., Ltd. describe DL-lactide based polyester as shape-memory biodegradable and absorbable materials. The polyester can be made into various articles that, upon heating, can recover their respective original shapes. However, the degradation of L-lactide based polyesters shows a non-linear mass loss leading to a sudden release of potentially acidic degradation products from the bulk material, that may cause a strong inflammatory response (K. Fu, D. W. Pack, A. M. Klibanov, R. S. Langer, Pharm Res 17:1, 100 (2000)). High crystallinity of oligomer particles slows down degradation at the end of the process and leads to the formation of fibrous capsules in vivo (K. A. Hooper, N. D. Macon, J. Kohn, J. Biomed. Mat. Res. 32,443 (1998)).
A challenge in endoscopic surgery is the tying of a knot with instruments and sutures currently available to close an incision or open lumen. It is especially difficult to manipulate the suture in a way that the wound lips are pressed together under the right stress. When the knot is fixed with a force that is too strong, necrosis of the surrounding tissue may occur (J. Hoer, U. Klinge, A. Schachtrupp, Ch. Töns, V. Schumpelick, Langenb. Arch. Surg 386, 218 (2001)). If the force is too weak, the formation of scar tissue which has poorer mechanical properties is observed, and may lead to the formation of hernias (N. C. F. Hodgson, R. A. Malthaner, T. Østbye, Ann. Surg. 231, 436 (2000)).
It is therefore an object of the present invention to provide a biodegradable shape memory polymeric device that can be formed in a compressed temporary shape and then on demand be expanded to its permanent shape to fit as required.
It is another object of the present invention to provide a biodegradable implant that has a linear mass degradation rate in vivo. It is a further object of the present invention to provide a biodegradable shape memory polymeric suture that can be formed in a compressed temporary shape and then on demand be expanded to its permanent shape to fit as required.
It is still a further object of the present invention to provide a biodegradable shape memory polymeric suture that can be knotted in a confined space.